AB1392 GENETICALLY PREDICTED APOLIPOPROTEIN B IN RELATION TO SYSTEMIC SCLEROSIS
Authors: X. Yang, Q. Dong, D. Wu, Q. Feng, J. Y. Chen, Q. Yu, P. F. He, X. Li, S. X. Zhang
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Systemic sclerosis (SSc) is an autoimmune disease characterized by progressive skin and internal organ fibrosis and has significant clinical sequelae [1]. Apolipoprotein B and E are found in two major subgroups of LDL [2]. Apolipoprotein E can be used as a predictor of SSc.[3] Apolipoprotein B is involved in autoimmunity [4]. However, whether apolipoprotein B is associated with SSc remains unestablished. <h3>Objectives</h3> We performed a two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between apolipoprotein B and SSc. <h3>Methods</h3> Statistics on apolipoprotein B were obtained from a genome-wide association study (GWAS) from the UK Biobank, which included 349,376 samples of European ancestry. A total of 182 single nucleotide polymorphisms (SNPs) were selected as genetic instruments, which satisfied linkage disequilibrium (r2 &lt; 0.001 and clump window &gt; 10,000 kb) and related to apolipoprotein B (P&lt;5×10-8). Summary-level data for SSc (107 cases and 218,499 controls) were derived from the FinnGen consortium. The inverse-variance weighted (IVW) method was used as the primary statistical model. The weighted median and MR-Egger regression were used as supplementary analyses to supplement the validation of IVW results. The Cochran Q-test was applied to check SNPs' statistical heterogeneity using MR-Egger estimates, with P &lt; 0.05 deemed significantly heterogeneous. The leave-one-out method was used to evaluate the effect of a single SNP on the causal association by excluding each SNP in turn. <h3>Results</h3> Genetically predicted apolipoprotein B was inversely associated with SSc risk (odds ratio (OR):0.51, 95% confidence interval (95% CI):0.26-0.98, P=0.04). MR-Egger also confirmed that apolipoprotein B was inversely associated with SSc risk (P=0.02). No heterogeneity was detected in Cochran's Q statistic. The intercept in the MR-Egger regression indicated no pleiotropy in any analysis (all P values&gt;0.05), suggesting this finding was reliable. Details of the results are shown in Fig. 1. <h3>Conclusion</h3> Apolipoprotein B is a protective factor for SSc, indicating that apolipoprotein B may be used as a component of drugs to treat SSc and slow down the development of SSc. <h3>References</h3> [1]Zhu JL, Black SM, Chen HW, Jacobe HT. Emerging treatments for scleroderma/systemic sclerosis. Fac Rev. 2021 May 5;10:43. doi: 10.12703/r/10-43. PMID: 34131653; PMCID: PMC8170563. [2]Lee DM, Alaupovic P. Apolipoproteins B, C-III and E in two major subpopulations of low-density lipoproteins. Biochim Biophys Acta. 1986 Nov 14;879(2):126-33. doi: 10.1016/0005-2760(86)90094-9. PMID: 3768392. [3]Young V, Ho M, Vosper H, Belch JJ, Palmer CN. Elevated expression of the genes encoding TNF-alpha and thromboxane synthase in leucocytes from patients with systemic sclerosis. Rheumatology (Oxford). 2002 Aug;41(8):869-75. doi: 10.1093/rheumatology/41.8.869. PMID: 12154203. [4]Marchini T, Abogunloko T, Wolf D. Modulating Autoimmunity against LDL: Development of a Vaccine against Atherosclerosis. Hamostaseologie. 2021 Dec;41(6):447-457. doi: 10.1055/a-1661-1908. Epub 2021 Dec 23. PMID: 34942658; PMCID: PMC8702296 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.